title: Tolerance induction by hair-specific keratins in murine alopecia areata.
abstract: AA is a presumptive autoimmune disease, severely damaging the hair follicle. Hair- and nail-specific keratins are discussed as potential candidates, which we controlled in C3H/HeJ mice that develop AA spontaneously or after skin transplantation. From nine keratins, K71 and K31 peptides supported T cell activation when presented by DCs to syngeneic naive T cells, and young C3H/HeJ mice receiving s.c. injections of peptide-loaded DC developed AA. The frequency of K71- and K31-specific CD4(+) and CD8(+) T cells increased four- to fivefold by vaccination, which corresponds with the frequency seen in skin transplantation-induced AA mice. Also, accessory molecule expression, the cytokine profile with a dominance of IFN-γ-expressing T cells, the proliferative response against AA lysate or peptide-loaded DCs, as well as peptide-specific cytotoxic T cells were similar in keratin peptide- and skin transplantation-induced AA. Instead, vaccination with soluble K71 or K31 peptides significantly retarded AA induction and prevented progression. Soluble peptide vaccination did not provoke immunosuppression but induced long-lasting T cell anergy with unresponsiveness to DC-presented K71 and K31 peptides. Thus, keratins K71 and K31 contribute to AA induction, and peptide application in a nonimmunogenic form serves as an efficient therapeutic.
authors.affiliation: 1.University Hospital of Surgery, Im Neuenheimer Feld 365, D 69120 Heidelberg, Germany. margot.zoeller@uni-heidelberg.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Erb
authors.forename: Pia
authors.initials: P
authors.lastname: Freyschmidt-Paul
authors.forename: Margot
authors.initials: M
authors.lastname: Zöller
mesh_terms: D000506:Alopecia Areata / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000276:immunology*; D053564:Keratins, Hair-Specific / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
chemical_list: D001324:Autoantigens; D053564:Keratins, Hair-Specific; D010455:Peptides
keywords: autoantigen; mouse; therapy; vaccination